Phenotypic Characteristics And Genetic Studies In A Patient With Goldenhar Syndrome

Background Goldenhar syndrome(GS),as a rare congenital anomaly,is characterized by a spectrum of phenotypic features,including ear anomalies,hemifacial microsomia,ocular defects,vertebral abnormalities,and other major organ system anomalies.Extreme variability of phenotypic manifestations is the main feature of the GS.The etiology of GS is inconclusive,which might be a muiltfactorial model.Methods Collection of medical history was performed with a 12-year-old boy presented to the hospital with complaints of malformed unilateral ear.Appearance abnormalities of the patient were found by visual inspection.Other potential malformations in the patient were found through chest x-ray,chest CT,and echocardiography.Then systematic use of high-throughput sequencing and gene set enrichment analysis was conducted to screen potential genetic etiology.Results The 12-year-Old male child was diagnosed with GS clinical features and other associated malformations:left pulmonary aplasia,atrial septal defect,and a duplication of the thumb on the right hand.Thirty concerned mutations were found through systematic use of high-throughput sequencing and gene set enrichment analysis.Conclusions A Goldenhar syndrome child associated with left pulmonary aplasia,atrial septal defect,and a duplication of the thumb has never been reported before.This study gave us a new understanding of clinical phenotype of GS.We also showed scientific and systematic method to find pathogenic genes and mutations,such as high-throughput sequencing combined with pathway analysis and Phenotype Based Gene Analyzer.